Overexpression of caveolin-1 in a human melanoma cell line results in dispersion of ganglioside GD3 from lipid rafts and alteration of leading edges, leading to attenuation of malignant properties
Overexpression of caveolin-1 in a human melanoma cell line results in dispersion of ganglioside GD3 from lipid rafts and alteration of leading edges, leading to attenuation of malignant properties
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DOI：
10.1111/j.1349-7006.2007.00419.x
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发表时间：
2007-04-01
期刊：
影响因子：
5.7
通讯作者：
Furukawa, Koichi
中科院分区：
文献类型：
--
作者：
Nakashima, Hideyuki;Hamamura, Kazunori;Furukawa, Koichi
Caveolin-1是脂筏的组成部分，被认为是一种肿瘤抑制分子。然而，小窝蛋白-1在癌细胞中发挥作用的机制还不清楚。我们使用人黑色素瘤细胞系（SK-MEL-28）产生小窝蛋白-1转染细胞（Cav-1（+）细胞），并研究小窝蛋白-1过表达对GD3介导的黑色素瘤恶性性质的影响。Cav-1（+）细胞的生长和运动性降低，p130Cas和桩蛋白的磷酸化水平降低。在漂浮分析中，虽然GD3主要定位于对照细胞中的糖脂富集微区（GEM）/筏，但其分散于Cav-1（+）细胞中的GEM/筏。相应地，Cav-1（+）细胞中的GD3在整个膜上均匀染色，而对照细胞显示膜的部分染色，可能在前缘。p130Cas和桩蛋白在前缘染色，并与对照细胞中的GD3共定位。与此相反，这些分子是弥漫性染色，没有明确的前沿检测到Cav-1（+）细胞。这些结果表明，小窝蛋白-1调节GD3介导的恶性信号通过改变GD3分布和前缘形成。这些结果揭示了小窝蛋白-1减少肿瘤细胞恶性特性的机制之一。
Caveolin-1 is a component of lipid rafts, and is considered to be a tumor suppressor molecule. However, the mechanisms by which caveolin-1 functions in cancer cells are not well understood. We generated caveolin-1 transfectant cells (Cav-1(+) cells) using a human melanoma cell line (SK-MEL-28) and investigated the effects of caveolin-1 overexpression on the GD3-mediated malignant properties of melanomas. Cav-1(+) cells had decreased cell growth and motility, and reduced phosphorylation levels of p130Cas and paxillin relative to controls. In floatation analysis, although GD3 was mainly localized in glycolipid-enriched microdomain (GEM)/rafts in control cells, it was dispersed from GEM/rafts in Cav-1(+) cells. Correspondingly, GD3 in Cav-1(+) cells stained uniformly throughout the membrane, whereas control cells showed partial staining of the membrane, probably at the leading edge. p130Cas and paxillin were stained in the leading edges and colocalized with GD3 in the control cells. In contrast, these molecules were diffusely stained and no definite leading edges were detected in Cav-1(+) cells. These results suggest that caveolin-1 regulates GD3-mediated malignant signals by altering GD3 distribution and leading edge formation. These results reveal one of the mechanisms by which caveolin-1 curtails the malignant properties of tumor cells.